Senior Research Fellowships in Clinical Science: people we've funded

This list includes current and past grantholders.

2017

Professor Matthew Burton

London School of Hygiene and Tropical Medicine

Severe corneal infections: prevention, diagnosis and treatment

Infection of the cornea caused by bacteria or fungi is a major and painful cause of blindness in low and middle-income countries. There are many challenges to the care of people with a cornea infection including delayed presentation, use of traditional eye medicine, limited training for health workers, limited availability and efficacy of anti-fungals and diagnostic uncertainty. Progressive corneal destruction is mediated by human and pathogen-derived enzymes (proteases) that destroy tissue and cause blindness.

Affordable, effective and readily available anti-fungal eye drops are needed. We will compare a simple formulation of chlorhexidine with the current standard care natamycin. Treatments to stop protease-mediated corneal destruction during infection are urgently needed. We will compare ilomastat with placebo eye drops in a trial, to stop holes developing in eyes. We will also use a cluster trial to see whether a combination of interventions together can prevent the delay to patients starting to take effective antimicrobials. The package includes giving chlorhexidine eye drops in the community and smartphone-assisted diagnosis, treatment and referral support. We will also evaluate which diagnostic tools are most useful in determining the type of infection.

Our findings could help improve prevention, diagnosis and treatment of corneal infections, reducing the rates of blindness in low and middle-income countries.

Professor Michael English

University of Oxford

Can a system intervention employing team-based case review help improve quality and safety of paediatric hospital care in Kenya?u

Many more children die in hospitals in Kenya often from treatable illnesses, compared with richer countries. Preventing deaths in very sick children requires health workers to act effectively in a team to initiate care rapidly and sustaining good care over time. When teams do not or cannot act effectively, mistakes can be made.

I aim to develop an approach in Kenya that helps healthcare teams reflect on events surrounding the death of a child in hospital and identify what needs to be changed. We will test the effect of the approach by comparing improvements in care in hospitals that use this approach with those that do not. We will develop a model that allows the insights found from reviewing deaths to be shared with teams, local and national managers and experts in child health so that care can be improved.

We will use the findings to understand the major problems in providing care to sick children and how they can be overcome. Our work aims to enable health systems to provide continuous, safe care in countries such as Kenya.

Dr Rashida Ferrand

London School of Hygiene and Tropical Medicine

Community-based interventions to improve HIV outcomes in adolescents: a cluster randomised trial in Zimbabwe

HIV is the leading cause of death among adolescents in Africa. There are many reasons for this, including difficulties in getting HIV testing and in taking treatment. Current HIV services are clearly not sufficient and additional strategies are required to help adolescents living with HIV to get diagnosed and to support them to take their HIV treatment. 

This project will evaluate an approach that incorporates HIV testing, facilitates linkage to HIV treatment services for adolescents (aged 12–20 years) who are HIV-positive, and provide support to improve their capacity to take HIV treatment. The intervention will be delivered in communities in Zimbabwe, where there is a high prevalence of HIV, and will complement existing services. We will carry out a trial to investigate whether the intervention is effective at improving the proportion of HIV-infected adolescents in the community whose HIV is well-controlled and investigate how cost-effective the intervention is in improving the number of years lived in full health by the participants. We will also evaluate how well the intervention is implemented.

Dr Simon Leedham

University of Oxford

Bone morphogenetic protein signalling and stromal-epithelial interaction in intestinal inflammation and carcinogenesis

Cancer is often described as the ‘wound that never heals’, and inflammation, wound repair and cancer are inextricably linked. This is because many of the chemical message networks that restrain and control epithelial stem cell growth in health are deranged in both wound repair and cancer. During regeneration, temporary signalling disruption from wounding allows cells to divide to replace those lost. With cancer, permanent disruption of signalling pathways leads to unrestrained cell division, one of the key hallmarks of malignancy. 

This project focuses on a key signalling pathway called bone morphogenetic protein (BMP). A team of gastroenterology scientists will use human tissue and biological models to explore how BMP signalling is temporarily disrupted during wound repair and to see how these important functions can be co-opted and corrupted by cancer. 

We aim to identify cells responsible for expression of BMP constituents in healthy tissue, wounds and cancer, to understand how this signalling pathway affects wound repair and tumour growth and to test potential new drugs that affect BMP signalling.  We will also use characteristic mutation patterns to identify human tumours that originate from BMP disruption and see if they behave differently to other cancers. 

Professor David Osrin

University College London

Community interventions for primary and secondary prevention of violence against women and girls: a cluster randomised controlled trial in urban India

There are high levels of violence towards women in India which causes physical, mental, societal, and economic harm. Reviews suggest community mobilisation could be a promising approach, but there have been few large trials that assess prevention programmes. 

We will test the effects of community mobilisation in slums in Mumbai,  with groups and volunteers who aim to prevent violence against women and girls. Our community intervention has been developed over 16 years of experience and two years of preparatory research, and our understanding of its effects is encapsulated in a theory of change. We will compare 24 areas receiving support services, activities from community groups and volunteers with 24 areas receiving support services only, primarily in terms of effects on occurrence of intimate partner violence and domestic violence over the course of a year. We will also examine disclosure of violence to support services, community attitudes to violence, bystander intervention, gender equality and the occurrence of sexual violence by non-partners. 

Our intervention is a replicable community-led action to address the public health burden of violence against women and girls, which is backed by public engagement and advocacy.

2016

Professor David Bennett 

University of Oxford

The mechanisms underlying sensory dysfunction in human pain channelopathies

Neuropathic pain is a common disabling pain state arising from injury to the sensory nervous system. Enhanced activity of sensory neurons, with lowered activation thresholds and spontaneous activity, is a key driver of neuropathic pain. Ion channels are proteins which regulate neuronal excitability. Rare inherited ion channel mutations can result in either reduced or increased pain sensitivity. Ion channel variants have also been linked with more common acquired neuropathic pain conditions such as painful neuropathy.

I will define the mechanisms by which mutations in ion channels alter the excitability of sensory neurons by studying how sensory stimuli are detected, transmitted and communicated by sensory neurons to other neurons. This will be achieved by studying patients with ion channel mutations to understand their perception of different sensory stimuli. I will develop models using cells derived from these patients in which ion channel function can be directly assessed. I will also develop animal models which mirror these same mutations.

My aim is to provide insight into how ion channels control sensory neuron excitability. This will aid diagnosis and management of rare inherited pain disorders and more common conditions such as painful diabetic neuropathy.

Professor Seena Fazel 

University of Oxford

Preventing violent crime and suicide in people with mental illness

The risks of violent crime and suicide are increased in people with schizophrenia spectrum disorders, bipolar disorder and depression. Although we understand more about the underlying causes for these risks, translating this knowledge into improvements for patient care requires more research into identifying high-risk groups and clarifying what treatments might prevent these outcomes.

I will investigate how to improve the assessment and reduce the risks of violent crime and suicide in people with mental illness. The approach I will take is to use large datasets that have been collected from real-world information on patients over many years. I will use research designs that account for socio-demographic and other background factors that differ between patients and others. As part of this, I will aim to develop reliable methods of assessment that could lead to effective interventions. I will also study what medications alter risks of violent crime and suicide in these patient groups, and also the effects of psychological and behavioural interventions in people with mental disorders under community criminal justice supervision. I would like to test whether these new approaches prevent violence and suicide in psychiatric patients and will investigate whether such a trial is feasible.

Dr Sinéad Langan

London School of Hygiene and Tropical Medicine

Using linked electronic health data to improve eczema diagnosis and outcomes

Eczema affects 5.8 million people in England, with 20% of children and up to 10% of adults affected – and this is becoming more common globally. Eczema is associated with major discomfort, stress and stigma and incurs significant healthcare costs. Eczema is commonly categorised into allergic and non-allergic subgroups, also known as phenotypes. It is clear that this separation is too simplistic. This poor categorisation of eczema subgroups limits our understanding of the causes, best treatments and our ability to predict future outcomes for patients. Recent studies also suggest that eczema may be associated with major health and social problems, including heart disease although the studies are small, lack important information or cannot assess timing.

I will use international health data to investigate the linked but distinct themes. I will use novel data and approaches to identify eczema subgroups. This work will help us target current and new treatments and predict long-term outcomes for patients. I will also assess the associations between eczema and major health-related problems (death, heart disease, and cancer), psychosocial, economic and social problems, such as depression, anxiety, reduced educational attainment/ income, marriage/partnership rates.

This work will inform the long-term care of patients with eczema.

Dr Rachel Lennon 

University of Manchester

Targeting force regulation to treat kidney disease

Each human kidney contains about a million tiny filters that enable the excretion of waste products from the body. Diseases that cause scarring of the filters can lead to kidney failure and there are no curative treatments. The filters contain specialised cells that create and are supported by a scaffold known as the glomerular basement membrane (GBM). In mice we found that GBM defects occur before there is evidence of kidney disease. We propose that these early defects start a process that leads to scarring of the filters and that this process is worsened by an inability of the specialised cells to respond to increased forces such as high blood pressure.

To test our hypothesis we will study mouse models of human kidney disease and human cells in culture. Using mass spectrometry and powerful microscopy we will define in great detail the progression of scarring in the kidney filters and how this responds to treatment with angiotensin-converting-enzyme (ACE) inhibitors which can slow the progression of kidney disease.

This research will find new explanations for how the filters scar and identify targets for new treatment. This could have significant impact on the early detection and treatment of kidney disease.

Professor Thomas Williams 

Imperial College London

The health consequences of genetic variants that have been selected by malaria, with a particular focus on polymorphisms affecting the red blood cell

Almost half of the world's population lives under the threat of malaria and it killed more than 400,000 people in 2015. Efforts to develop a vaccine have been disappointing and new approaches to control and treat malaria are badly needed. The existence of human genetic variants that provide natural protection against malaria has been recognised for more than 60 years. By studying such genes we stand to learn more about malaria and perhaps discover new ways to treat it. 

I will focus on four genes for which we have strong evidence of natural protection against malaria. All affect the red blood cell, the natural target of human infections. I will document their impact on malaria and other diseases through population studies in Kenya and observe their effects on rates of disease progression in adult volunteers who will be inoculated experimentally with live malaria parasites. I  will also study how they affect red cell function and investigate parasite invasion in the laboratory. 

By pinpointing the precise mechanisms for malaria resistance afforded by these genes we may be able to use them as a basis for drug and vaccine development.
 

2012-2015

| A | B | C | E | F | G | H | J | K | L | M | N | O | P | R | S | V | W |

A

Professor John Achermann

University College London

Novel mechanisms in adrenal and reproductive biology

Disorders of adrenal and gonad development are a diverse group of conditions that can be challenging to manage and potentially life-threatening. Professor Achermann's research focuses on: defining key molecular events involved in critical stages of adrenal and gonad development in humans; discovering novel causes of and diagnostic approaches to disorders (or differences) of sex development, ovarian insufficiency and adrenal hypoplasia; and exploring the ever-expanding role of steroidogenic factor 1 (NR5A1) in human disease. As well as having implications for the management of individuals with rare conditions, these studies are relevant for more common conditions such as infertility.

Dr Hashim Ahmed

University College London

Transforming the screening, diagnosis and treatment of prostate cancer

B

Professor David Bennett

University of Oxford

Injury and repair of the peripheral nervous system: the role of neuregulin-ErbB signalling

Professor Bennett employs a multidisciplinary approach, using techniques ranging from cellular models to patient cohorts, in order to gain a better understanding of how the peripheral nervous system responds to injury. His clinical interest in acquired and inherited peripheral neuropathies complements this research. His aim is to develop strategies to promote effective neural repair and prevent the development of deleterious consequences such as neuropathic pain. A key focus is the bi-directional signalling pathways between neurons and their associated glial cells which are essential for coordinating an effective response to neural injury. Professor Bennett's laboratory is currently focusing on the role of growth factors such as neuregulin in promoting neural repair.

Dr Sara Brown

University of Dundee

Molecular mechanisms in atopic skin

Atopic eczema is an itchy inflammatory skin disease which has increased in prevalence over recent decades. It is a complex trait arising from the interaction of multiple genetic and environmental factors, but eczema is highly heritable, demonstrating the importance of genetic predisposition. Multiple risk loci have been identified by genome-wide association studies, but a locus on chromosome 1q21 shows the strongest association. Within this locus, loss-of-function mutations in the FLG gene encoding the skin barrier protein filaggrin are well known to increase risk of atopic disease. Dr Brown has shown that copy number variation within FLG has a dose-dependent effect on eczema risk, and her current work aims to investigate whether related genes show a similar effect. She will also use organotypic skin culture to test the role of candidate genes/transcripts for which functional mechanisms remain to be defined. This work will move towards identifying targets for much-needed therapy development.

Dr Matthew Burton

London School of Hygiene and Tropical Medicine

Controlling blinding trachoma: intervention and pathophysiology studies for scarring disease in Ethiopia and Tanzania

Trachoma is the most common infectious cause of blindness worldwide. Chlamydia trachomatis triggers a scarring process in the conjunctiva, leading to the in-turning of eyelashes (trichiasis), which traumatises the cornea. Surgery can be performed to correct this and prevent blindness but results are mixed. Dr Burton's research focuses on improving the surgical treatment of trichiasis and understanding how this infection leads to tissue scarring. In Ethiopia, Dr Burton's team will conduct clinical trials comparing alternative treatment strategies. In Tanzania, a long-term cohort of children is being followed to investigate conjunctival immunofibrogenic responses that lead to scarring.

C

Dr Peter Campbell

Wellcome Trust Sanger Institute

Characterisation and analyses of cancer genomes using next-generation sequencing technologies

Dr Campbell is a haematologist with a research programme focused on cancer genomics. His specific areas of interest are the factors influencing the evolution of tumours, including mutational processes, selective pressures and environmental forces (such as drug therapy). Dr Campbell is also interested in developing translational applications of modern genomic technologies with the aim of improving health outcomes for patients with cancer.

Professor Patrick Chinnery

University of Cambridge

Genetic factors modulating the expression of mitochondrial disease

Professor Chinnery is a clinical neurologist with a specialist interest in inherited neurological diseases (neurogenetics). He studies the genetic and biochemical basis of inherited mitochondrial disorders based on one of the largest international cohorts of patients with these diseases. He has a major interest in understanding the relationship between genotype and phenotype, and particularly the basic mechanisms underpinning the inheritance of mitochondrial DNA mutations. He has also studied the role of common genetic variants of mitochondrial DNA in complex human traits, particularly Parkinson's disease. Professor Chinnery has an active translational research programme studying the natural history of mitochondrial diseases, and has conducted clinical trials to test the effects of new treatments for these disorders.

Dr Elizabeth Corbett

London School of Hygiene and Tropical Medicine

Community-wide TB case-finding linked to a nested cluster randomised trial of promotion of HIV-testing and prevention of HIV-related TB in Blantyre, Malawi

Dr Jenny Crinion

University College London

Mechanisms underlying spoken language production: facilitating frontal brain networks following aphasic stroke

Word-finding difficulty (anomia) is the most common and chronically disabling impairment following aphasic stroke. However, surprisingly little is understood about the contributions that individual frontal brain areas make to anomia recovery. The frontal language network overlaps considerably with those supporting other diverse cognitive functions such as cognitive control; both are likely involved in language learning and recovery. Dr Crinion’s research seeks to place spoken word production in the context of wider cognition to understand how common brain areas, and possibly common processes, support such disparate functions in the damaged brain. This will provide novel and fundamental insights into the mechanisms involved. To address these aims Dr Crinion will use whole-brain high-resolution structural and functional magnetic resonance imaging in conjunction with transcranial direct current stimulation, along with neuropsychological examination and behavioural training of aphasic patients. This provides a powerful platform to understand the causes of cognitive and spoken language change following brain damage.

E

Professor Alison Elliott

London School of Hygiene and Tropical Medicine

Helminths and allergy in Uganda

Professor Elliott is based in Uganda at the Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) Uganda Research Unit on AIDS, where she runs the Co-infection Studies Programme. She is interested in the effects of chronic immunomodulating infections on immune responses to vaccines and on infectious and allergic disease incidence. Her Fellowship supports both a birth cohort in which prenatal helminth exposure and treatment has been shown to influence eczema incidence, and a cluster randomised trial investigating the effects of intensive anthelminthic treatment among island fishing communities. Additionally, Professor Elliott is involved in building research capacity in Africa.

Dr Michael English

University of Oxford

Improving the ability of health systems to deliver essential hospital services: examining strategies targeting seriously ill children and newborns in Kenya

Dr English's research focuses on district hospitals, testing interventions hypothesised to improve the adoption of evidence-based paediatric practices specifically, and the quality of care more generally. He is working with the Kenyan Ministry of Health to develop a 'Clinical Information Network', which will generate a common clinical dataset spanning multiple hospitals. The data will be used to evaluate the effectiveness of performance feedback as an intervention; additional interventions will then be layered onto this platform to examine the effectiveness of multifaceted intervention strategies. Dr English's research team uses statistical, organisational and behavioural research methods to evaluate intervention effects and the relationships between context and mechanisms.

F

Professor Ismaa Sadaf Farooqi

University of Cambridge

Molecular and neural basis of obesity

Professor Farooqi is an endocrinologist who is using genetic strategies, including exome sequencing, to study over 5000 patients with severe obesity. Her team are discovering mutations in novel obesity genes, whose functions are studied using a range of molecular and cellular approaches; these proteins modulate neural circuits involved in the regulation of appetite. Professor Farooqi is also running a parallel programme of translational research to examine the role of the relevant molecules in eating behaviour, energy expenditure and peripheral metabolism. Her overall aim is to make a major contribution to the design of pharmacological interventions to benefit patients with severe obesity.

Dr Seena Fazel

University of Oxford

Risk factors for violent crime and repeat offending in severe mental illness

Dr Fazel is a psychiatrist investigating associations between severe mental illness and violent crime, and risk factors for adverse outcomes in psychiatric populations and prisoners. These studies are being undertaken in collaboration with the Karolinska Institutet and use high-quality Swedish national registers and genetically informed designs. In addition, research using English and Welsh prison data has clarified the extent of self-harm among prisoners and its relationship with suicide. Recently, Dr Fazel has been working to develop clinical prediction rules for high-risk groups in conjunction with the Medical Statistics Group at the University of Oxford. By applying epidemiological approaches to clinical uncertainties in psychiatry, Dr Fazel's aim is to gain insight into mechanisms for adverse outcomes and promising approaches to secondary prevention.

 

Professor Paul Fletcher

University of Cambridge

Complementary studies of learning and motivation in psychosis and pathological hyperphagia

Professor Fletcher uses combinations of cognitive challenges, neuroimaging and psychopharmacological manipulations to explore disturbances in learning, inference, motivation and decision making. His studies are aimed at furthering understanding of how perception and learning may be disrupted, both in the context of the abnormal beliefs and perceptions that characterise certain types of mental illness, and in association with health-harming behaviours such as overconsumption.

G

Dr Paul Gissen

University College London

The role of two key intracellular trafficking genes, VPS33B and VIPAR, in development and disease

Human deficiency of VPS33B and VIPAR leads to abnormalities in the development and function of multiple cells and organs, including the kidneys, liver and blood cells. Dr Gissen's group is investigating the molecular function of VPS33B and VIPAR, which form a complex involved in regulation of polarised trafficking of membrane proteins. The aim of the group's studies, which utilise cell and animal models of VPS33B and VIPAR deficiencies, is to delineate the protein interactome, changes in cell signalling and pathogeneses of disease changes. Specifically, Dr Gissen's research explores the characteristic abnormalities in endocytic recycling and their role in membrane formation and maintenance.

Professor Timothy Griffiths

Newcastle University

Cortical bases for auditory perception

Professor Griffiths's research concerns human complex-sound processing - the analysis of auditory patterns relevant to speech, music and environmental-sound analysis. He studies deficits in complex-sound processing in patients with brain lesions, using functional imaging data (fMRI and MEG) from normal subjects and depth electrode data from the auditory cortex of neurosurgical patients. The functional imaging is carried out at the Wellcome Trust Centre for Neuroimaging in London and the depth electrode data is acquired at the University of Iowa. These studies allow inferences to be made about normal complex-sound processing mechanisms. Other work explores abnormal complex-sound analysis in developmental and degenerative disorders, and brain mechanisms for tinnitus and auditory hallucinations.

Professor Ravindra Gupta

University College London

Genetics and biology of drug-resistant HIV

Of the 35 million people infected with HIV worldwide, 15 million are now receiving antiretroviral therapy - and this number is set to rise steeply following recommendations for universal treatment. Drug resistance arises commonly in resource-limited settings but goes largely undetected. Resistance to a core drug class, protease inhibitors, is poorly understood but probably involves multiple HIV genes. To date, scientific analyses have been limited to just one gene, protease, often using simple cell-line-based assays. It is now possible to sequence and generate whole viruses derived from patients in models of infection that more closely resemble in vivo conditions. This will allow detection of changes in virus resistance patterns with greater accuracy than ever before, with phenotypic evaluation of their impact in relevant models. This information will inform field tests designed to detect protease-inhibitor-resistant strains and help to plan strategy for further lines of antiretroviral therapy.

H

Dr Muzlifah Haniffa

Newcastle University

Functional proteomic analysis of innate immune subversion by human cytomegalovirus

Dr Haniffa is a dermatologist whose research programme focuses on understanding how dendritic cells, monocytes and macrophages, a family of cells collectively known as mononuclear phagocytes, regulate human immune responses. She will exploit functional genomics and comparative biology approaches to define the contribution of mononuclear phagocytes to peripheral-tissue homeostasis and immune responses during pathogen challenge, cancer and inflammation. Her overall aim is to develop new strategies to manipulate the host immune response to improve vaccine design and immunotherapy.

Professor Neil Hanley

University of Manchester

How does SOX9 regulate the pancreatic niche of beta cell differentiation?

Professor Hanley is a clinical endocrinologist who is interested in human embryogenesis and fetal development. With the advance of stem cell biology and the advent of induced pluripotent stem cell technology, it has become increasingly important to understand how normal human development unfolds, so that we can assess how faithfully stem cells are turned into mature cells in a dish. This makes detailed and direct analysis of human tissue at key stages of development an important consideration. Professor Hanley's award focuses on pancreatic development, and in particular the role of the transcription factor, SOX9. An emerging theme is that the lessons learned about SOX9 in this setting are informative in scenarios where SOX9 influences disease, such as fibrosis. Professor Hanley also hopes to take advantage of genome-wide technologies to gain broader insight into the molecular mechanisms that regulate human pancreatic development and wider embryogenesis.

Dr Neil Henderson

University of Edinburgh

An intravital imaging approach to elucidate novel mechanisms of organ fibrosis and repair

Organ fibrosis is a major global healthcare burden, playing a key pathophysiological role in many common diseases including cardiovascular disease, cancer, and chronic diseases of the liver, lung and kidney. However, there are currently no effective anti-fibrotic treatments. Dr Henderson is a hepatologist whose lab is interested in the cellular and molecular mechanisms that drive organ fibrogenesis, and also the pathways which are responsible for efficient wound healing and healthy tissue regeneration following injury. His current research focuses on the development of an intravital imaging approach to elucidate novel mechanisms of organ fibrosis and repair. By understanding more about how organs scar, heal and regenerate, Dr Henderson and his team hope to develop new treatments for patients with fibrotic diseases.

J

Dr Sam Janes

University College London

Defining the natural history of pre-invasive lung cancer lesions

K

L

M

Professor Helen McShane

University of Oxford

Evaluation of innovative TB vaccination strategies in preclinical and clinical models

TB remains a significant cause of mortality and morbidity throughout the world, and the emergence of drug-resistant strains of Mycobacterium tuberculosis means that the need for better global control of TB is more urgent than ever. Professor McShane's lab works on the design and delivery of innovative new vaccines, designing and testing vaccines in both preclinical animal models and then early-stage clinical trials. When successful, these early-stage trials lead into larger field studies through a network of collaborations across Africa. At present, Professor McShane's group is particularly interested in investigating human mycobacterial challenge models as a way to help select which vaccines should progress to efficacy testing in humans. Other interests of her group include aerosol routes of vaccine delivery, which are currently being evaluated in animal models and human clinical trials.

Dr Miratul Muqit

University of Dundee

Biochemical analysis of the PINK1-parkin signalling pathway in Parkinson's disease

Parkinson's disease is an incurable neurodegenerative movement disorder whose incidence is set to increase in the coming decades. Spectacular genetic advances have uncovered nearly 20 genes or loci associated with the development of Parkinson's. For instance, autosomal recessive mutations in genes encoding a protein kinase, PINK1, and a ubiquitin ligase, parkin, are causative of early-onset forms of Parkinson's. Until recently little was known about the biochemical properties of these enzymes and how they are regulated. Dr Muqit has recently elucidated a signalling pathway in which PINK1 phosphorylates parkin at a highly conserved residue (serine 65) within its ubiquitin-like domain, and has demonstrated that this leads to the activation of parkin E3 ligase activity. He plans to investigate how this pathway is regulated and to determine how its disruption leads to neurodegeneration in Parkinson's. It is hoped that a greater mechanistic understanding of this pathway will lead to novel ideas for better diagnosis and treatment of Parkinson's.

N

Dr James Nathan

University of Cambridge

The role of ubiquitin-binding proteins in the regulation of the ubiquitin-proteasome system

Dr Nathan is a respiratory physician whose research focuses on the regulation of protein degradation by the ubiquitin-proteasome system. All mammalian cells have to control their protein content to remove damaged proteins and regulate cell growth. Any disruption to cellular protein levels can lead to the rapid protein breakdown seen in muscle wasting, or uncontrolled growth and the accumulation of misfolded proteins that occurs in cancers and neurodegenerative conditions. The major mechanism for controlling intracellular protein levels is ubiquitination. A key question forming the basis of Dr Nathan's studies is how ubiquitinated proteins are differentially selected for degradation. He will use biochemical and genetic approaches to address this question, and aims to provide a better understanding of the ubiquitin system and to identify how proteins are efficiently delivered to the proteasome.

O

Professor David Osrin

University College London

Community interventions for primary and secondary prevention of violence against women and girls: a cluster randomised controlled trial in urban India

There are high levels of violence towards women in India which causes physical, mental, societal, and economic harm. Reviews suggest community mobilisation could be a promising approach, but there have been few large trials that assess prevention programmes. 

We will test the effects of community mobilisation in slums in Mumbai,  with groups and volunteers who aim to prevent violence against women and girls. Our community intervention has been developed over 16 years of experience and two years of preparatory research, and our understanding of its effects is encapsulated in a theory of change. We will compare 24 areas receiving support services, activities from community groups and volunteers with 24 areas receiving support services only, primarily in terms of effects on occurrence of intimate partner violence and domestic violence over the course of a year. We will also examine disclosure of violence to support services, community attitudes to violence, bystander intervention, gender equality and the occurrence of sexual violence by non-partners. 

Our intervention is a replicable community-led action to address the public health burden of violence against women and girls, which is backed by public engagement and advocacy.

P

Professor Matthew Pickering

Imperial College London

The pathophysiological role of complement regulation in disease

Complement refers to a system of proteins that play an important role in our ability to destroy pathogens such as bacteria. Complement recognises and destroys pathogens using a variety of techniques, and pathogens, in turn, utilise a number of strategies to avoid detection by complement. It is important that complement can distinguish between pathogens and our own tissues. This distinction is mediated by a group of proteins termed complement regulators. We now know that tissue injury in rare and common diseases is influenced by inappropriate complement activation due to defects in complement regulators. Professor Pickering's research unravels the mechanisms through which such tissue damage occurs and currently focuses on how complement can damage the kidney.

Dr Andrew Prendergast

Queen Mary, University of London

The impact of cotrimoxazole on healthy birth and growth in rural Zimbabwe

Undernutrition underlies 45 per cent of child deaths globally. Stunting, the most prevalent form of undernutrition, affects 165 million children under five years of age, leading to increased mortality from infections and impaired neurodevelopment. Annually, 20 million babies are born with low birth weight due to fetal growth restriction, prematurity, or both. Together, low birth weight, prematurity and stunting interact and overlap, contributing to an enormous number of child deaths and more pervasively hindering developmental potential. Dr Prendergast’s research focuses on new strategies to promote healthy birth and growth, by targeting inflammatory pathways that are common to preterm birth, intrauterine growth restriction and postnatal stunting. Building on the hypothesis that inflammation is driven predominantly by clinical and subclinical infections, abnormal microbiota composition and environmental enteric dysfunction, his group is undertaking a randomised clinical trial of cotrimoxazole, integrated with a package of nutrition interventions, among pregnant women and infants in rural Zimbabwe.

Professor Richard Price

University of Oxford

Optimising antimalarial combination therapies in an area coendemic for vivax and falciparum malaria

Professor Price's research programme focuses on the diagnosis, consequences and containment of multidrug-resistant malaria. Large-scale epidemiological field studies in Papua, Indonesia are defining the morbidity and mortality attributable to malaria, and assessing the impact and cost-effectiveness of adopting a unified treatment policy of artemisinin combination therapy for all species of the disease. Comparative clinical studies aim to identify a safe and effective radical cure for P. vivax. These clinical trials are complemented by laboratory studies looking to characterise drug-resistant malaria, through ex vivo drug susceptibility testing and genome-wide association studies.

R

Professor Geraint Rees

University College London

The conscious phenotype

Consciousness is central to the human condition, furnishing us with phenomenal awareness of the external world and the ability to reflect upon our own thoughts and experiences. Almost half our communication concerns the contents of our thoughts and experiences. The shared language we use to communicate these thoughts obscures the recent realisation that there is substantial variability in how different people experience the same physical environment. Professor Rees's research seeks to characterise the brain structures and mental processes that define this conscious phenotype, using brain imaging to study how such a phenotype may differ in neurodevelopmental disorders such as autism and to establish powerful new approaches to modifying the conscious phenotype using real-time fMRI.

Dr James Rowe

University of Cambridge

Optimisation of cognitive and behavioural control in Parkinson's disease and frontotemporal degeneration

Dr Rowe studies the cognitive physiology of neurodegenerative disease, including frontotemporal dementia, Parkinson’s disease and primary tauopathies. His Fellowship combines advances in magnetoencephalography and magnetic resonance imaging with computational modelling in order to measure the impact of disease and drugs on synaptic physiology in humans. The integration of brain imaging with psychopharmacology provides a powerful platform to understand the causes of cognitive and behavioural change in neurodegenerative disease, and also provides sensitive methods to evaluate the efficacy and mechanisms of novel therapeutics.

S

Dr David Savage

University of Cambridge

Lipodystrophy: a paradigm for elucidating pathogenic mechanisms in the metabolic syndrome

Obesity is a major global health problem, primarily due to strong links between the condition and a range of highly prevalent metabolic disorders, including insulin resistance, type 2 diabetes, fatty liver disease, dyslipidaemia and polycystic ovary syndrome. Dr Savage's lab focuses on obesity's relationship to metabolic disease. Uniquely, the lab's research focuses on patients with inherited forms of lipodystrophy, a rare disease in which people lack all or some body fat. Paradoxically, these patients manifest almost exactly the same metabolic problems as obese people. These patients are being studied to assist in identifying the genetic basis of their disease, to enable a precise diagnosis, and to facilitate genetic screening in the relatives of those with the disease. Additionally, the identification of these novel human monogenic diseases often leads to novel insights into the biology and physiological relevance of the genes or proteins involved, and what is found in a rare disease may be very relevant to more prevalent conditions in the metabolic syndrome.

Professor Anthony Scott

London School of Hygiene and Tropical Medicine

Population impact of a conjugate vaccine on pneumococcal transmission and disease in Kenya

Vaccines protect the individuals receiving them, but they can also have additional helpful or detrimental effects at the population level. Professor Scott is investigating the impact of a pneumococcal conjugate vaccination at the population level in Kenya. Working at the KEMRI-Wellcome Trust Research Programme in Kilifi, he is linking episodes of pneumococcal disease in hospital with immunisation events in clinics, recording this data on a continuously updated register of the resident population (around 270 000 people). His study aims to measure the protection experienced by unvaccinated individuals, along with the extent to which the reduction in transmission of pneumococcal strains targeted by the vaccine is offset by an increase in transmission of non-vaccine strains.

Dr Robert Semple

University of Cambridge

Genetic dissection of mechanisms linking cell dysfunction, insulin resistance and major human disease

Dr Semple is an endocrinologist whose research seeks to elucidate the mechanisms underlying human insulin resistance and how insulin resistance drives pandemic diseases such as type 2 diabetes, fatty liver and subfertility. He focuses on rare, severe disorders of growth and insulin action, encompassing insulin resistance, insulin supersensitivity, dwarfism and overgrowth. He follows identification of single gene defects with targeted studies in cells, model organisms (including mice), and humans. His particular focuses at present are on activating and inhibitory mutations in the phosphatidylinositol 3-kinase/AKT signalling pathway, and on syndromes featuring severe insulin resistance due to genetic defects created during mitosis or DNA damage repair.

Professor Liam Smeeth

London School of Hygiene and Tropical Medicine

Exploiting the potential offered by the increasing computerisation of health records for population-based research

The increasing computerisation of health records offers tremendous opportunities for research - both for observational research and for intervention trials embedded in clinical care. Professor Smeeth is focusing on exploiting this potential to assess drug effects and to investigate disease aetiology. A major focus of his research is cardiovascular disease, with one area of particular interest being the causal role of infections and inflammation. While there is strong evidence that inflammation plays an important role in cardiovascular disease, translating this knowledge into improved healthcare has proved challenging. The major factor hindering this translation is a lack of knowledge drawn from humans in real-world clinical settings, which is a challenge Professor Smeeth aims to overcome.

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Dr George Vassiliou

Wellcome Trust Sanger Institute

Interactions between co-occuring leukaemogenic mutations identified in acute myeloid leukaemia genomes

Dr Vassiliou is a consultant haematologist and leads the Haematological Cancer Genetics group at the Sanger Institute. His group studies the pathogenesis and treatment of haematological malignancies with a particular focus on acute myeloid leukaemia. Additionally, the group develops and applies novel molecular methodologies for the diagnosis, classification and treatment of haematological cancers.

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Dr Sarah Walmsley

University of Sheffield

Regulation of neutrophilic inflammation by the HIF-PHD pathway

Dr Walmsley is a respiratory physician with a research focus on how oxygen sensing and metabolic regulation influence phagocyte host defence. Through a better understanding of the mechanisms by which hypoxia regulates key neutrophil functions and survival responses, Dr Walmsley aims to validate the therapeutic potential of selective manipulation of these pathways in patients with chronic neutrophil-dominant inflammatory lung diseases such as COPD.

Dr Michael Weekes

University of Cambridge

Functional proteomic analysis of innate immune subversion by human cytomegalovirus

Dr Weekes is an infectious diseases physician whose research focuses on the evasion of innate immunity by intracellular pathogens. His lab aims to identify and characterise novel antiviral restriction factors. He has developed new functional proteomic approaches that enable systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection. Applied to human cytomegalovirus (HCMV), an important pathogen in neonates and immunosuppressed people, these technologies revealed how HCMV orchestrates the expression of more than 8,000 cellular proteins to manipulate intrinsic, innate and adaptive immune defences in addition to host signalling and metabolism. His lab is currently using proteomic and biochemical approaches to characterise the function and mechanism of action of the most important novel restriction factors identified, in addition to developing new screens to examine restriction of HCMV and other intracellular pathogens in greater depth.

Professor Robert Wilkinson

Imperial College London

Quadruple intervention against tuberculosis

HIV and TB are among the most pressing public health problems in Africa. Through its studies, Professor Wilkinson's group has revealed that by early adulthood more than 80 per cent of people in African townships are infected with TB. The group has investigated the effects and mechanisms of preventative therapies, including antiretroviral therapy, isoniazid preventative therapy (IPT) and vitamin D provision. Interestingly, severe vitamin D deficiency is highly prevalent among black Africans and is associated with HIV-TB. A clinical trial of antiretrovirals (ART) for the prevention of TB versus a trial of ART plus IPT showed that IPT reduced the incidence of tuberculosis by 37 per cent in HIV-infected individuals on ART, findings that have already been incorporated into national and WHO policies.

Professor Thomas Williams

Imperial College London

The health consequences of inherited red blood cell disorders in Kenya

Professor Williams is a clinical scientist who works on the burden and clinical consequences of red cell genetic disorders. The main focus of Professor Williams's research has been the relationship between specific red cell defects (including sickle-cell trait and alpha-thalassaemia) and malaria, a subject he has approached through both epidemiological and laboratory-based mechanistic studies conducted at the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya. Recently, Professor Williams has also been studying the adverse consequences of haemoglobin disorders in African children, with a focus on sickle-cell disease and G6PD deficiency.

People we've funded

Many of our grantholders carry out research in Africa and Asia. See our directories: